title: A dominant connexin43 mutant does not have dominant effects on gap junction coupling in astrocytes.
abstract: Dominant mutations in GJA1, the gene encoding the gap junction protein connexin43 (Cx43), cause oculodentodigital dysplasia (ODDD), a syndrome affecting multiple tissues, including the central nervous system (CNS). We investigated the effects of the G60S mutant, which causes a similar, dominant phenotype in mice (Gja1(Jrt/+)). Astrocytes in acute brain slices from Gja1(Jrt/+) mice transfer sulforhodamine-B comparably to that in their wild-type (WT) littermates. Further, astrocytes and cardiomyocytes cultured from Gja1(Jrt/+) mice showed a comparable transfer of lucifer yellow to those from WT mice. In transfected cells, the G60S mutant formed gap junction (GJ) plaques but not functional channels. In co-transfected cells, the G60S mutant co-immunoprecipitated with WT Cx43, but did not diminish GJ coupling as measured by dual patch clamp. Thus, whereas G60S has dominant effects, it did not appreciably reduce GJ coupling.
authors.affiliation: Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6077, USA. swasseff@mail.med.upenn.edu
authors.forename: Sameh
authors.initials: S
authors.lastname: Wasseff
authors.forename: Charles K
authors.initials: CK
authors.lastname: Abrams
authors.forename: Steven S
authors.initials: SS
authors.lastname: Scherer
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000502:physiology* / Q000648:ultrastructure; D001703:Biophysics; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D018920:Coculture Techniques; D018031:Connexin 43 / Q000235:genetics*; D004558:Electric Stimulation; D017629:Gap Junctions / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D047468:Immunoprecipitation; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D017434:Protein Structure, Tertiary / Q000235:genetics; D014162:Transfection
chemical_list: D018031:Connexin 43; C543076:GJA1 protein, mouse; D005904:Glial Fibrillary Acidic Protein; D049452:Green Fluorescent Proteins